Radiant source imaging (for example bioluminescence or fluorescence imaging) may be used in in vivo diagnostic studies on animal or human subjects in the areas of medical research, pathology and drug discovery and development, diagnosis, etc. Bioluminescence may be generated by cells that have been transfected with a luminescent label such as luciferase. It may also be used to label molecules of interest. As such it may be used as a marker to indicate a specific tissue type, monitor physiological function, track the movement or distribution of drugs or medicaments, track the distribution of a therapeutic compound administered to the subject, or changes associated with the progression of a disease.
Light from radiant energy sources is strongly scattered in most tissue structures of interest. In addition, tissue structures often contain absorbers. Despite the scattering and absorption, some light can be detected on the surface of a tissue structure. Luminescent imaging systems and methods (e.g., Bioluminescence tomography or “BLT”) have been developed that can record the spatial distribution of light emitted from the surface of the subject and used to calculate distribution of sources within the tissue structure.
BLT is an imaging modality that makes use of bioluminescent markers that emit light in response to predefined biochemical environments. The emission of light can be used to detect molecular processes associated with the development of diseases. BLT is used in preclinical experiments using small animals to study various disease processes and drug effects. BLT recovers the spatial distribution of bioluminescence inside the medium from measured intensities on the tissue surface.
Most reconstruction methods developed to date rely on the diffusion approximation (DA) to the equation of radiative transfer (ERT). The DA converts the difficult-to-solve integro-differential ERT into a partial-differential diffusion equation (DE) for which various analytical solution and stable numerical methods exist. The DA is accurate if the absorption coefficient of the medium under consideration is low relative to the scattering coefficient. The approximation becomes less accurate in media with small geometries where boundary effects are dominant, or in fluid-filled, void-like regions. These adverse conditions generally hold in small animal bioluminescence imaging where bioluminescent sources such as luciferases are employed as a light-emitting probe. Such probes have a broad emission spectrum that peaks between 460 nm and 630 nm where intrinsic tissue absorption may be high. Furthermore, the optical path length in small animals, (e.g., mice and rats) is relatively small and boundary effects dominate.